PB2267: TRIAL IN PROGRESS: PHASE 3 TRIAL EVALUATING THE EFFICACY AND SAFETY OF ODRONEXTAMAB VERSUS INVESTIGATOR’S CHOICE IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (OLYMPIA-1)
Authors: Stefano Luminari, Tae Min Kim, Ashish Risal, Manjusha Namuduri, Jingxian Cai, Bertha Fearon-Chalet, Min Zhu, Sushmita Mukherjee, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Umberto Vitolo
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: A proportion of patients with follicular lymphoma (FL) progress within 2 years of receiving standard first-line treatment with rituximab (R)-based chemoimmunotherapy (CIT), leading to suboptimal long-term outcomes. Odronextamab is an off-the-shelf CD20×CD3 bispecific antibody that showed antitumor activity as monotherapy in the Phase 2 ELM-2 study in patients with relapsed/refractory (R/R) FL: overall and complete response (CR) rates were 82% and 75%, respectively, median duration of response 20.5 months, and median progression-free survival (PFS) 20.2 months, as assessed by independent central review (ICR). With an optimized step-up regimen, odronextamab had a generally manageable safety profile with infrequent treatment-related adverse events leading to treatment discontinuation (7.6%) (Kim, et al. ASH, 2022). In the R/R setting, many patients have been exposed to multiple lines of therapy and potential long-term toxicity, whereas in the first-line setting patients may have better responses to T-cell engagers due to more intact immune system without T-cell exhaustion. Given the promising Phase 2 results and the potential of improved response in first-line, investigation of odronextamab monotherapy in previously untreated FL is supported. Aims: The OLYMPIA-1 trial aims to evaluate the efficacy and safety of odronextamab versus investigator’s choice of CIT in patients with previously untreated FL. Methods: OLYMPIA-1 is a Phase 3, open-label, randomized, multicenter trial of odronextamab versus CIT (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]; rituximab, cyclophosphamide, vincristine, prednisone [R-CVP]; or rituximab-bendamustine) in previously untreated FL. The study consists of Part 1 (safety run-in), followed by Part 2 (randomization) which evaluates odronextamab versus investigator’s choice of CIT. In Part 1, odronextamab intravenous (IV) infusion is administered in a step-up regimen during Cycle (C) 1 to mitigate the risk of cytokine release syndrome, with a full dose to be administered from C2. Patients with CR or partial response at the end of induction will receive odronextamab for up to 12 doses or until disease progression, loss to follow-up, or withdrawal of consent, whichever is earlier. In Part 2, patients will be randomized 1:1 to receive induction of 6 cycles of odronextamab followed by odronextamab maintenance, or CIT followed by rituximab maintenance. Patients aged 18 years and older with CD20-positive FL (Grade 1–3a, stage II bulky, or stage III/IV), measurable disease, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–2 are eligible. Exclusion criteria include central nervous system lymphoma or leptomeningeal lymphoma and histological evidence of transformation to high-grade or diffuse large B-cell lymphoma. Results: The primary endpoint in Part 2 is CR at 30 months (CR30) as assessed by the ICR, with key secondary endpoints of PFS (ICR-assessed), event-free survival (ICR-assessed), investigator-assessed CR30, and patient-reported physical function as measured by change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30). An estimated 200 sites globally will participate to enroll 12–24 patients in Part 1 and up to 446 patients in Part 2. Summary/Conclusion: This Phase 3 trial will determine the utility of odronextamab monotherapy compared with CIT as a first-line treatment for patients with previously untreated FL.Keywords: Non-Hodgkin’s lymphoma, Follicular lymphoma, Bispecific, Phase III